This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The divalent metal ion transporter (DMT1) is a member of the SoLute Carrier (SLC) group of membrane transport proteins. DMT1 proteins are found in all kingdoms of life and depending on the species transport iron and manganese but also other trace elements like copper, cadmium and nickel. Transport is fueled by proton symport taking advantage of the electrochemical proton gradient across the membrane. The structure of DMT will provide information about the proton- driven transport mechanism of divalent metal ion uptake into cells. The obtained structural and mechanistic insights will help to explain mutations associated with diseases and guide the discovery of DMT1 inhibitors or activators.